A general strategy will be explored for designing novel proteins that self- assemble into large symmetrical structures, including nanoparticle cages, filaments, layers, and porous crystalline materials. The method makes use of natural oligomeric proteins, genetically fused in precise arrangement. The present proposal is to fully explore this new area of symmetric protein design we will validate the method and test its limitations by designing and experimentally characterizing a series of assemblies with a wide range of architectures. Beyond the potential future applications in materials science, the principles underlying these assemblies will be used to illuminate and guide experiments on some natural protein assemblies. Genomic studies will uncover potentially uncharacterized protein complexes that have evolved by acquiring multiple oligomerization domains. The quaternary structure and symmetry of interesting candidates will be investigated by biophysical and crystallographic methods. Finally, fiber forming proteins, such as the amyloid protein transthyretin, will be studied by chemical cross-linking and EPR methods to see what role symmetry may play in filamentous assemblies.